Chimeric Antigen Receptors that Recognize Mesothelin for Cancer ImmunotherapyChimeric antigen receptors (CARs) with high affinity for mesothelin that can be used as an immunotherapy to treat cancers that express mesothelin, such as pancreatic cancer, ovarian cancer, and mesothelioma. The technology includes CAR constructs with one of three different mesothelin-specific antibody portions, including either the mouse-derived SS or SS1 antibody fragments or the human HN1 antibody fragment.
Mesothelin is a protein cancer antigen with limited expression on normal cells that is overexpressed by cancer cells. CARs are hybrid proteins consisting of an antibody portion that recognizes a cancer antigen, such as a mesothelin-specific antibody, fused to receptor signaling domains that serve to activate the CAR-expressing cell to kill tumor cells. Cells that express CARs, most notably T cells, are highly reactive against their specific tumor antigen in an MHC-unrestricted manner to generate an immune response that promotes robust tumor cell elimination when infused into cancer patients. Infusion of cells expressing these mesothelin-specific CARs into patients could prove to be a powerful new immunotherapeutic tool for treating various cancers that express mesothelin.
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